Soluble ST2 release from airway epithelial cells is suppressed by house dust mite and the miRNA-29 family

<bold>Background and aim:</bold> IL-33 and its receptor ST2 are closely associated with asthma. The miRNA-29 family (miR-29s) have been implicated in the regulation of IL-33 through soluble ST2 (sST2) release. We have previously observed overexpression of miR-29s in bronchial biopsies from asthmatic individuals. In this study we aimed to examine the involvement of miR-29s and allergic airway inflammation in the modulation of sST2 in airway epithelial cells. <bold>Methods:</bold> Wild-type C57BL/6J mice were sensitized and challenged intranasally with house dust mite (HDM; n=5) or administered PBS (n=4) as controls. RNA was extracted from isolated mouse trachea and miR-29 expression was analyzed by RT-qPCR. Primary human bronchial epithelial cells (HBECs) were stimulated with HDM or transfected with miR-29 mimics or inhibitors and the secretion of sST2 was measured after 24 or 48h in cell supernatants using ELISA. <bold>Results:</bold> <italic>In vivo</italic> exposure to HDM tended to increase the expression of miR-29b-3p and miR-29c-3p in mouse trachea. Levels of sST2 were significantly reduced in supernatants from HBECs after stimulation with HDM in submerged (p<0.01) and air-liquid interface (ALI) cultures (p<0.05). Transfection of submerged HBECs with a miR-29b mimic reduced sST2 in cell supernatants (p<0.01), whereas inhibiting miR-29b resulted in a tendency towards enhanced sST2 release in supernatants from ALI-HBECs (p=0.067). <bold>Conclusion:</bold> Suppression of the IL-33 decoy receptor sST2 by HDM and miR-29s in airway epithelial cells may promote IL-33/ST2-signalling in the airways. Thus, our data suggest a potential role for miR-29s in exacerbating IL-33-dependent allergic airway inflammation.